Tetraflagellochloris mauritanica gen. et sp. nov. (Chlorophyceae), a New Flagellated Alga from the Mauritanian Desert: Morphology, Ultrastructure, and Phylogenetic Framing.
Morphological, ultrastructural, and molecular-sequence data were used to assess the phylogenetic position of a tetraflagellate green alga isolated from soil samples of a saline dry basin near F'derick, Mauritania. This alga can grow as individual cells or form non-coenobial colonies of up to 12 individuals. It has a parietal chloroplast with an embedded pyrenoid covered by a starch sheath and traversed by single parallel thylakoids, and an eyespot located in a parietal position opposite to the flagellar insertion. Lipid vacuoles are present in the cytoplasm. Microspectroscopy indicated the presence of chlorophylls a and b, with lutein as the major carotenoid in the chloroplast, while the eyespot spectrum has a shape typical of green-algal eyespots. The cell has four flagella, two of them long and two considerably shorter. Sequence data from the 18S rRNA gene and ITS2 were obtained and compared with published sequences for green algae. Results from morphological and ultrastructural examinations and sequence analysis support the placement of this alga in the Chlorophyceae, as Tetraflagellochloris mauritanica L. Barsanti et A. Barsanti, gen. et sp. nov.


3D Stacked Construct: A Novel Substitute for Corneal Tissue Engineering.
Corneal trauma/injury often results in serious complications including permanent vision loss or loss of visual acuity which demands corneal transplantations or treatment with allogenic graft tissues. There is currently a huge shortage of donor tissue worldwide and the need for human corneal equivalents increases annually. In order to meet such demand the current clinical approach of treating corneal injuries is limited and involves synthetic and allogenic materials which have various shortcomings when it comes to actual transplantations. In this study we introduce the newly developed, next generation of our previously established 3D self-assembled constructs, where multiple constructs are grown and stacked on top of each other without any other artificial product. This new technology brings our 3D in vitro model closer to what is seen in vivo and provides a solid foundation for future studies on corneal biology.Lipids are known for playing a vital role during metabolism and diseased state of various tissues and Sphingolipids are one such class of lipids which are involved in various cellular mechanisms and signaling processes. The impacts of Sphingolipids that have been documented in several human diseases often involve inflammation, neovascularization, tumorigenesis, and diabetes, but these conditions are not yet thoroughly studied. There is very little information about the exact role of Sphingolipids in the human cornea and future studies aiming at dissecting the mechanisms and pathways involved in order to develop novel therapies. We believe that our novel 3D stacked model can be used to delineate the role of Sphingolipids in the human cornea and provide new insights for understanding and treating various human corneal diseases.


Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide and currently has the fastest rising incidence of all cancers. Sorafenib was originally identified as an inhibitor of multiple oncogenic kinases and remains the only approved systemic therapy for advanced HCC. However, acquired resistance to sorafenib has been found in HCC patients, which results in poor prognosis. Here, we show that metallothionein (MT)-1G is a critical regulator and promising therapeutic target of sorafenib resistance in human HCC cells. The expression of MT-1G messenger RNA and protein is remarkably induced by sorafenib but not other clinically relevant kinase inhibitors (e.g., erlotinib, gefitinib, tivantinib, vemurafenib, selumetinib, imatinib, masitinib, and ponatinib). Activation of the transcription factor nuclear factor erythroid 2-related factor 2, but not p53 and hypoxia-inducible factor 1-alpha, is essential for induction of MT-1G expression following sorafenib treatment. Importantly, genetic and pharmacological inhibition of MT-1G enhances the anticancer activity of sorafenib in vitro and in tumor xenograft models. The molecular mechanisms underlying the action of MT-1G in sorafenib resistance involve the inhibition of ferroptosis, a novel form of regulated cell death. Knockdown of MT-1G by RNA interference increases glutathione depletion and lipid peroxidation, which contributes to sorafenib-induced ferroptosis. These findings demonstrate a novel molecular mechanism of sorafenib resistance and suggest that MT-1G is a new regulator of ferroptosis in HCC cells. (Hepatology 2016;64:488-500).


[Keynote address to the 19th congress of ALANAM].
In his keynote address to the international seminar of the ALANAM (Association of Latin American National Academies of Medicine), held October 28-30, 2010, in Santiago, Chile, Dr. Alejandro Goic, President of the Chilean Academy of Medicine, discussed the state of health and of medical and health research in Latin American countries. He called attention to the fact that the National Academies of Medicine are learned and honorific institutions whose main function is to reflect on, and foster, medical practice, medical education, and public health. He noted that medical doctors bear a great individual and collective responsibility in the organization and management of sanitary services, but that health care as such concerns all citizens. Poverty is one of the most important factors conditioning the state of health in any society, particularly in developing countries. Because of the very nature of the medical profession, doctors are acquainted not only with the physical and mental ailments that afflict the poor, but also with their precarious housing, income, and labor conditions, as well as with how difficult it is for them to have access to good health care and education. He emphasized that health care is not only a technical, administrative and economic institution, but a moral one as well. When the economic considerations of the health care industry and its financial mechanisms prevail over the medical needs of the general population, a severe social problem arises to the extent that important segments of the population are denied access to health care, and preventable human suffering is left unattended. Society and governments have the responsibility of financing health services and ensure that the humanitarian ends of medicine are met in health care services and sanitary institutions. The superior aim in health care should always be to afford a humane, caring, and respectful relationship between health care professionals and all users of the health care system without exception.


Light-induced changes of the circadian clock of humans: increasing duration is more effective than increasing light intensity.
To evaluate the effect of increasing the intensity and/or duration of exposure on light-induced changes in the timing of the circadian clock of humans. Multifactorial randomized controlled trial, between and within subject design General Clinical Research Center (GCRC) of an academic medical center 56 healthy young subjects (20-40 years of age) Research subjects were admitted for 2 independent stays of 4 nights/3 days for treatment with bright or dim-light (randomized order) at a time known to induce phase delays in circadian timing. The intensity and duration of the bright light were determined by random assignment to one of 9 treatment conditions (duration of 1, 2, or 3 hours at 2000, 4000, or 8000 lux). Treatment-induced changes in the dim light melatonin onset (DLMO) and dim light melatonin offset (DLMOff) were measured from blood samples collected every 20-30 min throughout baseline and post-treatment nights. Comparison by multi-factor analysis of variance (ANOVA) of light-induced changes in the time of the circadian melatonin rhythm for the 9 conditions revealed that changing the duration of the light exposure from 1 to 3 h increased the magnitude of light-induced delays. In contrast, increasing from moderate (2,000 lux) to high (8,000 lux) intensity light did not alter the magnitude of phase delays of the circadian melatonin rhythm. Results from the present study suggest that for phototherapy of circadian rhythm sleep disorders in humans, a longer period of moderate intensity light may be more effective than a shorter exposure period of high intensity light.


Features of atherosclerosis in patients with angina and no obstructive coronary artery disease.
An association between atherosclerosis and coronary vasospasm has previously been suggested. However, to date, no conclusive data on the whole spectrum of these disorders have been published. This study aimed to define specific morphological features of atherosclerosis in patients with angina and no obstructive coronary artery disease (ANOCA) due to coronary vasospasm. From February 2019 to January 2020, we enrolled 75 patients referred to our laboratory for a coronary function test (CFT) due to ANOCA and suspected coronary vasomotor dysfunction. The CFT consisted of an acetylcholine test and a physiology assessment with hyperaemic indexes using adenosine. Patients were divided into two groups according to the presence or absence of coronary vasospasm triggered by acetylcholine (ACH+ and ACH-, respectively). In addition, optical coherence tomography (OCT) was performed to assess the lipid index (LI), a surrogate for lipid area, and the prevalence of markers of plaque vulnerability. ACH+ patients had a higher LI than ACH- patients (LI: 819.85 [460.95-2489.03] vs 269.95 [243.50-878.05], respectively, p=0.03), and a higher prevalence of vulnerable plaques (66% vs 38%, p=0.04). Moreover, ACH+ patients showed a higher prevalence of neovascularisation compared to ACH- subjects (37% vs 6%, p=0.02) and a trend towards a higher prevalence of all individual markers, in particular thin-cap fibroatheroma (20% vs 0%, p=0.06). No differences were detected between patterns of coronary vasospasm. The presence of coronary vasospasm, regardless of its phenotype, is associated with higher lipid burden, plaque vulnerability and neovascularisation.


The logic of adjunctive therapy in surgical patients with resectable cancer.
The principles and rationale of using multiple modalities (surgery, chemotherapy, radiotherapy, and immunotherapy) to treat solid malignancies is reviewed. Animal models of human tumors have clearly demonstrated the superiority of combining local treatment (eg, surgery) with systemic treatment (eg, chemotherapy). Although the results of many trials of adjunctive therapy in man are still preliminary, they warrant the caustious generalization that multiple modality therapy will increasingly become more effective than surgery alone for most types of solid tumors. Although the strategy of employing adjunctive therapy is rational, it must be emphasized that the therapeutic efficacy of specific drugs or agents for particular patients or tumor types has not always been satisfactory. Clinical trials now in progress may demonstrate more effective regimens. In the meantime, physicians should be cautious about using adjunctive therapy as standard treatment until long-term benefits and safety have been demonstrated. Participation in clinical trials is encouraged to verify the validity and application of this therapeutic approach.


Loss of radioactivity in radiocesium-bearing microparticles emitted from the Fukushima Dai-ichi nuclear power plant by heating.
Radiocesium-bearing microparticles (CsPs) substantially made of silicate glass are a novel form of radiocesium emitted from the broken containment vessel of Fukushima Dai-ichi nuclear power plant. CsPs have a potential risk of internal radiation exposure caused by inhalation. Radiation-contaminated waste including CsPs is being burned in incinerators; therefore, this study has investigated the responses of CsPs to heating in air. The radioactivity of CsPs gradually decreased from 600 °C and was almost lost when the temperature reached 1000 °C. The size and spherical morphology of CsPs were almost unchanged after heating, but cesium including radiocesium, potassium and chlorine were lost, probably diffused away from the CsPs. Iron, zinc and tin originally dissolved in the glass matrix were crystallized to oxide nanoparticles inside the CsPs. When the CsPs were heated together with weathered granitic soil that is common in Fukushima, the radiocesium released from CsPs was sorbed by the surrounding soil. From these results, it is expected that the radioactivity of CsPs will be lost when radiation-contaminated waste including CsPs is burned in incinerators.


Ni/NiO Exsolved Perovskite La0.2Sr0.7Ti0.9Ni0.1O3-δ for Semiconductor-Ionic Fuel Cells: Roles of Electrocatalytic Activity and Physical Junctions.
A semiconductor-ionic fuel cell (SIFC) is recognized as a promising technology and an alternative approach to reduce the operating temperature of solid oxide fuel cells. The development of alternative semiconductors substituting easily reduced transition metal oxide is a great challenge as high activity and durability should be satisfied simultaneously. In this study, the B-site Ni-doped La0.2Sr0.7Ti0.9Ni0.1O3-δ (LSTN) perovskite is synthesized and used as a potential semiconductor for SIFC. The in situ exsolution and A-site deficiency strategy enable the homogeneous decoration of Ni/NiO nanoparticles as reactive sites to improve the electrode reaction kinetics. It also supports the formation of basic ingredient of the Schottky junction to improve the charge separation efficiency. Furthermore, additional symmetric Ni0.8Co0.15Al0.05LiO2-δ (NCAL) electrocatalytic electrode layers significantly enhance the electrode reaction activity and cells' charge separation efficiency, as confirmed by the superior open circuit voltage of 1.13 V (close to Nernst's theoretical value) and peak power density of 650 mW cm-2 at 550 °C, where the latter is one order of magnitude higher than NCAL electrode-free SIFC. Additionally, a bulk heterojunction effect is proposed to illustrate the electron-blocking and ion-promoting processes of the semiconductor-ionic composite electrolyte in SIFCs, based on the energy band values of the applied materials. Overall, we found that the energy conversion efficiency of novel SIFC can be remarkably improved through in situ exsolution and intentional introduction of the catalytic functionality.


Sister chromatid exchange in Philadelphia chromosome (Ph1)-positive leukemia.
The sister chromatid exchange (SCE) frequency was studied in the leukemic cells of 12 patients, 10 with Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML), 1 with Ph1-negative CML, and 1 with acute myeloblastic leukemia. Except for two patients in the blastic phase of CML, the SCE values were within the normal range [3.8 +/- 6.4 (S.D.) SCE/cell; normal is 3.3 +/- 2.2 SCE/cell]. In the two cases with the blastic phase of CML, the values were 7.6 +/- 3.2 and 8.9 +/- 4.7 SCE/cell, a statistically significant difference from the control values. However, in the patient with acute myeoblastic leukemia, the SCE incidence increased from 3.6 to 24.4 SCE per cell when therapy was changed to daunorubicin and vincristine and the disease became progressive. Further studies on SCE and leukemia may prove the usefulness of this determination for therapeutic and clinical purposes.


Providing a phylogenetic framework for trait-based analyses in brown algae: Phylogenomic tree inferred from 32 nuclear protein-coding sequences.
In the study of the evolution of biological complexity, a reliable phylogenetic framework is needed. Many attempts have been made to resolve phylogenetic relationships between higher groups (i.e., interordinal) of brown algae (Phaeophyceae) based on molecular evidence, but most of these relationships remain unclear. Analyses based on small multi-gene data (including chloroplast, mitochondrial and nuclear sequences) have yielded inconclusive and sometimes contradictory results. To address this problem, we have analyzed 32 nuclear protein-coding sequences in 39 Phaeophycean species belonging to eight orders. The resulting nuclear-based phylogenomic trees provide virtually full support for the phylogenetic relationships within the studied taxa, with few exceptions. The relationships largely confirm phylogenetic trees based on nuclear, chloroplast and mitochondrial sequences, except for the placement of the Sphacelariales with weak bootstrap support. Our study indicates that nuclear protein-coding sequences provide significant support to conclusively resolve phylogenetic relationships among Phaeophyceae, and may be a powerful approach to fully resolve interordinal relationships with increased taxon sampling.


The physiological consequences of crib-biting in horses in response to an ACTH challenge test.
Stereotypies are repetitive and relatively invariant patterns of behavior, which are observed in a wide range of species in captivity. Stereotypic behavior occurs when environmental demands produce a physiological response that, if sustained for an extended period, exceeds the natural physiological regulatory capacity of the organism, particularly in situations that include unpredictability and uncontrollability. One hypothesis is that stereotypic behavior functions to cope with stressful environments, but the existing evidence is contradictory. To address the coping hypothesis of stereotypies, we triggered physiological reactions in 22 horses affected by stereotypic behavior (crib-biters) and 21 non-crib-biters (controls), using an ACTH challenge test. Following administration of an ACTH injection, we measured saliva cortisol every 30 min and heart rate (HR) continuously for a period of 3h. We did not find any differences in HR or HR variability between the two groups, but crib-biters (Group CB) had significantly higher cortisol responses than controls (Group C; mean ± SD: CB, 5.84 ± 2.62 ng/ml, C, 4.76 ± 3.04 ng/ml). Moreover, crib-biters that did not perform the stereotypic behavior during the 3-hour test period (Group B) had significantly higher cortisol levels than controls, which was not the case of crib-biters showing stereotypic behavior (Group A) (B, 6.44 ± 2.38 ng/ml A, 5.58 ± 2.69 ng/ml). Our results suggest that crib-biting is a coping strategy that helps stereotypic individuals to reduce cortisol levels caused by stressful situations. We conclude that preventing stereotypic horses from crib-biting could be an inappropriate strategy to control this abnormal behavior, as it prevents individuals from coping with situations that they perceive as stressful.


Antibody-Mediated Targeting of the FGFR1c Isoform Increases Glucose Uptake in White and Brown Adipose Tissue in Male Mice.
The increased prevalence of obesity and its cardiometabolic implications demonstrates the imperative to identify novel therapeutic targets able to effect meaningful metabolic changes in this population. Antibody-mediated targeting of fibroblast growth factor receptor 1c isoform (FGFR1c) has been shown to ameliorate hyperglycemia and protect from diet- and genetically-induced obesity in rodents and nonhuman primates. However, it is currently unknown which tissue(s) contribute to this glucose-lowering effect. Thus, to elucidate this effect, we treated euglycemic mice with H7, a monoclonal antibody that selectively targets FGFR1c, and used whole-body positron emission computed tomography with a glucose tracer (18F-fluorodeoxyglucose). Treatment with H7 increased basal glucose uptake in white adipose tissue (WAT), brown adipose tissue (BAT), the brain, and liver but reduced it in the quadriceps muscles. Consequentially, blood glucose was significantly reduced in response to treatment. Under insulin-stimulated conditions, the effects of H7 were maintained in WAT, BAT, liver, and muscle. Treatment with H7 decreased triglyceride (TG) content and increased adipose TG lipase content in white adipose tissue, while increasing activation of acetyl coenzyme A carboxylase, suggesting futile cycling of TGs, albeit favoring net hydrolysis. We demonstrated, in vitro, this is a direct effect of treatment in adipose tissue, as basal cellular respiration and glucose uptake were increased in response to treatment. Taken together, these data suggest that antibody-mediated targeting of FGFR1c exerts its powerful glucose-lowering efficacy primarily due to increased glucose uptake in adipose tissue.


Bioequivalence assessment of two formulations of ibuprofen.
This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz(®), produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen(®), manufactured by Boots Company, Nottingham, UK. A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen.


Cationic polymer synergizing with chemotherapeutics and re-purposing antibiotics against cancer cells.
Chemotherapy is one of the most effective treatments for cancer. However, toxicity and the development of drug resistance have become the major hurdles to the commonly used chemotherapeutics such as doxorubicin and paclitaxel. Antibiotics have also been used as anti-cancer drugs due to their anti-proliferative and cytotoxic effects. However, these anti-tumor antibiotics like ciprofloxacin face the similar resistance and toxicity issues. In this study, we used a quaternary ammonium-functionalized cationic polycarbonate to synergize with the existing chemotherapeutics and re-purpose antibiotics to address the resistance and toxicity issues. When used in combination with the drugs, the cationic polymer induced 2-3 fold more damage in the cancer cell membrane within 2 hours, thus enhancing the uptake of chemotherapeutics up to 2.5 fold more into the breast, liver and even chemotherapeutics-resistant cancer cells. On the other hand, the chemotherapeutics increased the cellular uptake of polymer. The combined effects resulted in 3-10 fold reduction in IC50 of chemotherapy drugs and yielded therapeutic synergy at a clinically-relevant concentration range of drugs when treating multiple types of cancer cells, while the use of guanidinium-functionalized polymer capable of membrane translocation did not lead to a synergistic effect. Thus, the quaternary ammonium-functionalized cationic polymer can increase the therapeutic efficacies of existing drugs, mitigating toxicities by lowering required dosage and circumventing drug resistance via its membrane disruption mechanism. The findings of this study provide insights into designing future anticancer therapy.


Functional capacity of XRCC1 protein variants identified in DNA repair-deficient Chinese hamster ovary cell lines and the human population.
XRCC1 operates as a scaffold protein in base excision repair, a pathway that copes with base and sugar damage in DNA. Studies using recombinant XRCC1 proteins revealed that: a C389Y substitution, responsible for the repair defects of the EM-C11 CHO cell line, caused protein instability; a V86R mutation abolished the interaction with POLbeta, but did not disrupt the interactions with PARP-1, LIG3alpha and PCNA; and an E98K substitution, identified in EM-C12, reduced protein integrity, marginally destabilized the POLbeta interaction, and slightly enhanced DNA binding. Two rare (P161L and Y576S) and two frequent (R194W and R399Q) amino acid population variants had little or no effect on XRCC1 protein stability or the interactions with POLbeta, PARP-1, LIG3alpha, PCNA or DNA. One common population variant (R280H) had no pronounced effect on the interactions with POLbeta, PARP-1, LIG3alpha and PCNA, but did reduce DNA-binding ability. When expressed in HeLa cells, the XRCC1 variants-excluding E98K, which was largely nucleolar, and C389Y, which exhibited reduced expression-exhibited normal nuclear distribution. Most of the protein variants, including the V86R POLbeta-interaction mutant, displayed normal relocalization kinetics to/from sites of laser-induced DNA damage: except for E98K and C389Y, and the polymorphic variant R280H, which exhibited a slightly shorter retention time at DNA breaks.


DNA methylation detection: recent developments in bisulfite free electrochemical and optical approaches.
DNA methylation is one of the significant epigenetic modifications involved in mammalian development as well as in the initiation and progression of various diseases like cancer. Over the past few decades, an enormous amount of research has been carried out for the quantification of DNA methylation in the mammalian genome. Earlier, most of these methodologies used bisulfite treatment. However, the low conversion, false reading, longer assay time and complex chemical reaction are the common limitations of this method that hinder their application in routine clinical screening. Thus, as an alternative to bisulfite conversion-based DNA methylation detection, numerous bisulfite-free methods have been proposed. In this regard, electrochemical biosensors have gained much attention in recent years for being highly sensitive yet cost-effective, portable, and simple to operate. On the other hand, biosensors with optical readouts enable direct real time detection of biological molecules and are easily adaptable to multiplexing. Incorporation of electrochemical and optical readouts into bisulfite free DNA methylation analysis is paving the way for the translation of this important biomarker into standard patient care. In this review, we provide a critical overview of recent advances in the development of electrochemical and optical readout based bisulfite free DNA methylation assays.


Effects of lowering the minimum alcohol purchasing age on weekend assaults resulting in hospitalization in New Zealand.
We estimated the effects on assault rates of lowering the minimum alcohol purchasing age in New Zealand from 20 to 18 years. We hypothesized that the law change would increase assaults among young people aged 18 to 19 years (the target group) and those aged 15 to 17 years via illegal sales or alcohol supplied by older friends or family members. Using Poisson regression, we examined weekend assaults resulting in hospitalization from 1995 to 2011. Outcomes were assessed separately by gender among young people aged 15 to 17 years and those aged 18 to 19 years, with those aged 20 and 21 years included as a control group. Relative to young men aged 20 to 21 years, assaults increased significantly among young men aged 18 to 19 years between 1995 and 1999 (the period before the law change), as well as the postchange periods 2003 to 2007 (incidence rate ratio [IRR] = 1.21; 95% confidence interval [CI] = 1.05, 1.39) and 2008 to 2011 (IRR = 1.20; 95% CI = 1.05, 1.37). Among boys aged 15 to 17 years, assaults increased during the postchange periods 1999 to 2003 (IRR = 1.28; 95% CI = 1.10, 1.49) and 2004 to 2007 (IRR = 1.25; 95% CI = 1.08, 1.45). There were no statistically significant effects among girls and young women. Lowering the minimum alcohol purchasing age increased weekend assaults resulting in hospitalization among young males 15 to 19 years of age.


The spatial clustering of obesity: does the built environment matter?
Obesity rates in the USA show distinct geographical patterns. The present study used spatial cluster detection methods and individual-level data to locate obesity clusters and to analyse them in relation to the neighbourhood built environment. The 2008-2009 Seattle Obesity Study provided data on the self-reported height, weight, and sociodemographic characteristics of 1602 King County adults. Home addresses were geocoded. Clusters of high or low body mass index were identified using Anselin's Local Moran's I and a spatial scan statistic with regression models that searched for unmeasured neighbourhood-level factors from residuals, adjusting for measured individual-level covariates. Spatially continuous values of objectively measured features of the local neighbourhood built environment (SmartMaps) were constructed for seven variables obtained from tax rolls and commercial databases. Both the Local Moran's I and a spatial scan statistic identified similar spatial concentrations of obesity. High and low obesity clusters were attenuated after adjusting for age, gender, race, education and income, and they disappeared once neighbourhood residential property values and residential density were included in the model. Using individual-level data to detect obesity clusters with two cluster detection methods, the present study showed that the spatial concentration of obesity was wholly explained by neighbourhood composition and socioeconomic characteristics. These characteristics may serve to more precisely locate obesity prevention and intervention programmes.


Tunable Nonreciprocal Quantum Transport through a Dissipative Aharonov-Bohm Ring in Ultracold Atoms.
We report the experimental observation of tunable, nonreciprocal quantum transport of a Bose-Einstein condensate in a momentum lattice. By implementing a dissipative Aharonov-Bohm (AB) ring in momentum space and sending atoms through it, we demonstrate a directional atom flow by measuring the momentum distribution of the condensate at different times. While the dissipative AB ring is characterized by the synthetic magnetic flux through the ring and the laser-induced loss on it, both the propagation direction and transport rate of the atom flow sensitively depend on these highly tunable parameters. We demonstrate that the nonreciprocity originates from the interplay of the synthetic magnetic flux and the laser-induced loss, which simultaneously breaks the inversion and the time-reversal symmetries. Our results open up the avenue for investigating nonreciprocal dynamics in cold atoms, and highlight the dissipative AB ring as a flexible building element for applications in quantum simulation and quantum information.


Iterative reverse Monte Carlo and molecular statics for improved atomic structure modeling: a case study of zinc oxide grown by atomic layer deposition.
Reverse Monte Carlo (RMC) modeling is a common method to derive atomic structure models of materials from experimental diffraction data. However, conventional RMC modeling does not impose energetic constraints and can produce non-physical local structures within the simulation volume. Although previous strategies have introduced energetic constraints during RMC modeling, these approaches have limitations in computational cost and physical accuracy. In this work, we periodically introduce molecular statics (MS) energy minimizations during RMC modeling in an iterative RMC-MS approach. We test this iterative RMC-MS approach using diffraction data collected by in operando high energy X-ray diffraction during atomic layer deposition of ZnO as a sample case. For MS relaxations we employ ReaxFF pair potentials previously established for ZnO. We find that RMC-MS and RMC provide equivalent agreement with experimental data, but RMC-MS structures are on average 0.6 eV per atom lower in energy and are more consistent with known ZnO atomic structure features. The iterative RMC-MS approach we report can accommodate large systems with minimal additional computational burden beyond a standard RMC simulation and can leverage established pair potentials for immediate application to study a wide range of materials.


Self-sustainable protonic ceramic electrochemical cells using a triple conducting electrode for hydrogen and power production.
The protonic ceramic electrochemical cell (PCEC) is an emerging and attractive technology that converts energy between power and hydrogen using solid oxide proton conductors at intermediate temperatures. To achieve efficient electrochemical hydrogen and power production with stable operation, highly robust and durable electrodes are urgently desired to facilitate water oxidation and oxygen reduction reactions, which are the critical steps for both electrolysis and fuel cell operation, especially at reduced temperatures. In this study, a triple conducting oxide of PrNi0.5Co0.5O3-δ perovskite is developed as an oxygen electrode, presenting superior electrochemical performance at 400~600 °C. More importantly, the self-sustainable and reversible operation is successfully demonstrated by converting the generated hydrogen in electrolysis mode to electricity without any hydrogen addition. The excellent electrocatalytic activity is attributed to the considerable proton conduction, as confirmed by hydrogen permeation experiment, remarkable hydration behavior and computations.


BRCA1-induced apoptosis involves inactivation of ERK1/2 activities.
Mutation in the BRCA1 gene is associated with an increased risk of breast and ovarian cancer. Recent studies have shown that the BRCA1 gene product may be important in mediating responses to DNA damage and genomic instability. Previous studies have indicated that overexpression of BRCA1 can induce apoptosis or cell cycle arrest at the G(2)/M border in various cell types. Although the activation of JNK kinase has been implicated in BRCA1-induced apoptosis, the role of other members of the mitogen-activated protein kinase family in mediating the cellular response to BRCA1 has not yet been examined. In this study, we monitored the activities of three members of the MAPK family (ERK1/2, JNK, p38) in MCF-7 breast cancer cells and U2OS osteosarcoma cells after their exposure to a recombinant adenovirus expressing wild type BRCA1 (Ad.BRCA1). Overexpression of BRCA1 in MCF-7 cells resulted in arrest at the G(2)/M border; however, BRCA1 expression in U2OS cells induced apoptosis. Although BRCA1 induced JNK activation in both cell lines, there were marked differences in ERK1/2 activation in response to BRCA1 expression in these two cell lines. BRCA1-induced apoptosis in U2OS cells was associated with no activation of ERK1/2. In contrast, BRCA1 expression in MCF-7 cells resulted in the activation of both ERK1/2 and JNK. To directly assess the role of ERK1/2 in determining the cellular response to BRCA1, we used dominant negative mutants of MEK1 as well as MEK1/2 inhibitor PD98059. Our results indicate that inhibition of ERK1/2 activation resulted in increased apoptosis after BRCA1 expression in MCF-7 cells. Furthermore, BRCA1-induced apoptosis involved activation of JNK, induction of Fas-L/Fas interaction, and activation of caspases 8 and 9. The studies presented in this report indicate that the response to BRCA1 expression is determined by the regulation of both the JNK and ERK1/2 signaling pathways in cells.


Mental search of concepts is supported by egocentric vector representations and restructured grid maps.
The human hippocampal-entorhinal system is known to represent both spatial locations and abstract concepts in memory in the form of allocentric cognitive maps. Using fMRI, we show that the human parietal cortex evokes complementary egocentric representations in conceptual spaces during goal-directed mental search, akin to those observable during physical navigation to determine where a goal is located relative to oneself (e.g., to our left or to our right). Concurrently, the strength of the grid-like signal, a neural signature of allocentric cognitive maps in entorhinal, prefrontal, and parietal cortices, is modulated as a function of goal proximity in conceptual space. These brain mechanisms might support flexible and parallel readout of where target conceptual information is stored in memory, capitalizing on complementary reference frames.


Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia.
Thirty-eight patients with primary resistant or relapsing acute myeloid leukemia (AML) were treated with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). Median age was 41 (range 11-70). Sixteen patients had AML that was primary resistant to induction treatment, while 22 were relapsed, 11 after autologous bone marrow transplant (AuBMT), 8 less than 6 months from complete remission (CR) achievement, and 3 were second relapse from chemotherapy alone. Overall, 21 of 38 patients (55%) obtained CR. Age, sex, length of CR, and interval between autoBMT and FLAG administration did not significantly influence the CR rate. On the contrary, a normal karyotype at diagnosis was significantly related to a better outcome. There were 4 induction deaths (10%), due to fungal infection in 2 patients and hemorrhagic complications in the remaining two. All patients experienced profound cytopenia. Median time to neutrophil (>500/microl) recovery was 21 days, while a platelet count >20,000/microl was reached after 23 days. The median period of hospitalization was 31 days. The nonhematological toxicity was mild, mainly consisting of mucositis. There were 17 documented infections and 17 episodes of fever of unknown origin. Following CR achievement, 6 patients received autoBMT, 3 alloBMT, 2 high-dose arabinosil-cytosine, and 2 are on a waiting list for transplantation procedure. We conclude that FLAG is an effective and well-tolerated regimen for refractory or recurrent AML, mainly useful for patients to be admitted to bone marrow transplantation.


Association of a Combination of Sarcopenia and Type 2 Diabetes with Blood Parameters, Nutrient Intake, and Physical Activity: A Nationwide Population-Based Study.
This study aimed to investigate the association of sarcopenia and type 2 diabetes (T2D) with blood parameters, nutrient intake, and physical activity in older Korean adults. We divided 2952 participants into four groups: sarcopenic diabetes (SD), sarcopenia alone (S), diabetes alone (D), and non-sarcopenia and non-diabetes (NSND). Sarcopenia was defined by the appendicular skeletal muscle mass index, and T2D by fasting glucose levels or ongoing treatment. Blood samples were collected after an 8-h fast. Nutrient intake was assessed using a 24-h recall; physical activity was evaluated using a questionnaire. Compared with those in the other groups, the men in the S and SD groups showed significantly lower hemoglobin and hematocrit levels; vitamin D levels in men and parathyroid hormone levels in women were significantly lower in the SD group. Total energy, protein, and carbohydrate intakes were significantly lower in the SD and S groups than those in the D and NSND groups. Physical inactivity was significantly more common in the SD group (men: odds ratio, 1.61; women: odds ratio, 2.37) than in the NSND group. A combination of sarcopenia and diabetes as well as sarcopenia alone was associated with low levels of blood parameters, poor nutrient intake, and low physical activity.


Treatment for Lexical Retrieval Impairments in Primary Progressive Aphasia: A Research Update with Implications for Clinical Practice.
Lexical retrieval impairments (also known as anomia or word-finding deficits) are an early and prominent symptom in primary progressive aphasia (PPA), causing distress and frustration to individuals with PPA and their communication partners, and prompting research on lexical retrieval treatment. This paper reviews the research on lexical retrieval treatment in PPA from the earliest reports in the 1990s to early 2018 and considers the implications of this research for clinical practice. The number of published studies has increased markedly over the past decade, consisting primarily of behavioral studies, with rapid recent growth in noninvasive brain stimulation studies. Five general treatment techniques were identified in the behavioral studies, described here as standard naming treatment, Look, Listen, Repeat treatment, cueing hierarchies, semantically focused treatments, and lexical retrieval in context. Across techniques, behavioral studies targeting difficult-to-retrieve items typically report immediate gains, and there is evidence these gains can be maintained over months to years by some participants who continue with long-term treatment. There is also evidence that prophylactic treatment supports retrieval of treated items compared with untreated items. There is limited evidence for generalization of treatment to untreated items, suggesting the primary aim of lexical retrieval treatment in this population is to maintain retrieval of a core vocabulary for as long as possible. Language and cognitive assessment and piloting of the intended treatment can inform decisions about treatment selection and participant suitability for long-term lexical retrieval treatment. The paper concludes with some questions to guide clinical decision making about whether to implement or continue with a behavioral lexical retrieval treatment.


Neural mirroring and social interaction: Motor system involvement during action observation relates to early peer cooperation.
Whether we hand over objects to someone, play a team sport, or make music together, social interaction often involves interpersonal action coordination, both during instances of cooperation and entrainment. Neural mirroring is thought to play a crucial role in processing other's actions and is therefore considered important for social interaction. Still, to date, it is unknown whether interindividual differences in neural mirroring play a role in interpersonal coordination during different instances of social interaction. A relation between neural mirroring and interpersonal coordination has particularly relevant implications for early childhood, since successful early interaction with peers is predictive of a more favorable social development. We examined the relation between neural mirroring and children's interpersonal coordination during peer interaction using EEG and longitudinal behavioral data. Results showed that 4-year-old children with higher levels of motor system involvement during action observation (as indicated by lower beta-power) were more successful in early peer cooperation. This is the first evidence for a relation between motor system involvement during action observation and interpersonal coordination during other instances of social interaction. The findings suggest that interindividual differences in neural mirroring are related to interpersonal coordination and thus successful social interaction.


Intraspecific diversity of Brevibacterium linens, Corynebacterium glutamicum and Rhodococcus erythropolis based on partial 16S rDNA sequence analysis and Fourier-transform infrared (FT-IR) spectroscopy.
The intraspecific diversity of 31 strains of Brevibacterium linens, 27 strains of Corynebacterium glutamicum and 29 strains of Rhodococcus erythropolis was determined by partial 16S rDNA sequence analysis and Fourier-transform infrared (FT-IR) spectroscopy. As a prerequisite for the analyses, 27 strains derived from culture collections which had carried invalid or wrong species designations were reclassified in accordance with polyphasic taxonomical data. FT-IR spectroscopy proved to be a rapid and reliable method for screening for similar isolates and for identifying these actinomycetes at the species level. Two main conclusions emerged from the analyses. (1) Comparison of intraspecific 16S rDNA similarities suggested that R. erythropolis strains have a very low diversity, B. linens displays high diversity and C. glutamicum occupies an intermediate position. (2) No correlation of FT-IR spectral similarity and 16S rDNA sequence similarity below the species level (i.e. between strains of one species) was observed. Therefore, diversification of 16S rDNA sequences and microevolutionary change of the cellular components detected by FT-IR spectroscopy appear to be de-coupled.


Genome-Wide Profiling of DNA Methyltransferases in Mammalian Cells.
Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is currently the method of choice to determine binding sites of chromatin-associated factors in a genome-wide manner. Here, we describe a method to investigate the binding preferences of mammalian DNA methyltransferases (DNMT) based on ChIP-seq using biotin-tagging. Stringent ChIP of DNMT proteins based on the strong interaction between biotin and avidin circumvents limitations arising from low antibody specificity and ensures reproducible enrichment. DNMT-bound DNA fragments are ligated to sequencing adaptors, amplified and sequenced on a high-throughput sequencing instrument. Bioinformatic analysis gives valuable information about the binding preferences of DNMTs genome-wide and around promoter regions. This method is unconventional due to the use of genetically engineered cells; however, it allows specific and reliable determination of DNMT binding.


Palisaded encapsulated neuroma--a classic presentation of a commonly misdiagnosed neural tumor.
We present a case report of a classical presentation of palisaded encapsulated neuroma (PEN) of the skin occurring on the nasolabial crease and a review of the literature. A young woman presented with a smooth lobulated papule on the cheek enlarging over 2 years. Histologic examination revealed a well-circumscribed dermal nodule of small spindle cells with wavy nuclei arranged in fascicles, consistent with the diagnosis of PEN. PEN is a previously described, benign cutaneous neural tumour, with a histological appearance between that of a neurofibroma and a schwannoma. Though not uncommon, PEN remains under-diagnosed by many pathologists. Clinically, PEN is most commonly misdiagnosed as a basal cell carcinoma, a nevus, or as a neurofibroma.


[Schizotypal personality disorder--diagnosis and treatment].
Schizotypal personality disorder is relatively common disorder, and is considered to be a mild form of schizophrenia. It is characterized by such "psychotic" symptoms as ideas of reference, odd or magical thinking, perceptual illusions and an inappropriate or flattened affect. In their contact with others, patients show odd expression and behavior. Since, numerous schizotypal symptoms can be treated successfully with atypical antipsychotic medication, the patient should be referred to a psychiatrist or neurologist. The mainstay of psychotherapy consists in crisis management, development of self-awareness of the problem, breaking down social isolation and general unspecific support in coping with daily problems.


Antimicrobial agents, triclosan, chloroxylenol, methylisothiazolinone and borax, used in cleaning had genotoxic and histopathologic effects on rainbow trout.
Triclosan (TRC), chloroxylenol (PCMX) and methylisothiazolinone (MIT) have been commonly used as an antimicrobial in soaps while borax (BRX) is used in household cleaning. After using these chemicals, they are washed down drains and getting into the aquatic ecosystem in which they may affect aquatic living organisms. In the present study, the chronic effects of TRC, PCMX, MIT and BRX on genotoxicity, gene expression and histopathology of rainbow trout (Oncorhynchus mykiss) were evaluated for 40 days under semi static condition. The comet assay results indicated that MIT, TRC and PCMX caused significant DNA damage to erythrocytes of the fish. Transcription of SOD, GPX1, GPX2, GSTA, HSP90BB, HSP90BA, CAT, and HSC70A genes were significantly regulated as a result of TRC, PCMX, MIT, and BRX exposure except PCMX exposed GSTA gene. Histological lesions were detected in gills, spleen liver, and trunk kidney of the fish. Lamellar fusion, hyperplasia and epithelial necrosis in gills, melanomacrophage centers and splenic necrosis in spleen, pyknotic nucleus, fat vacuoles, necrotic hepatocytes in liver, cloudy swelling in the tubules, renal tubule epithelial cells degeneration, glomerular capillaries dilation and glomerulus degeneration in kidney, were observed. Our study demonstrates the chronic toxic effect of TRC, PCMX, MIT, and BRX is high in rainbow trout. Therefore, we should be more careful when using these chemicals for cleaning in order to protect aquatic environment.


Epizootiological observations on canine microfilaremia in Gujarat state, India.
The present investigation was conducted to study the prevalence of microfilaremia in dogs in Gujarat. A total of 418 adult dogs aged between 2 and 14 years with signs of weakness and non-specified complaints, presented at TVCC, Deesa (North Gujarat), Nandini Veterinary Hospital, Surat (South Gujarat), and Private Clinics, Ahmedabad (Central Gujarat), were included in the present investigation for studying the prevalence of microfilaremia from July 2016 to May 2017. A total of 418 dogs were screened, of which 33 were found positive for circulating microfilariae with the prevalence rate of 7.89% in the population. Among microfilaremic dogs, the finding of microfilariae of Dipetalonema (Acanthocheilonema) reconditum was more common (23 cases; 69.69%) than Dirofilaria immitis (10 cases; 30.30%) making their prevalence in the population of 418 dogs as 5.50% and 2.39%, respectively. Breed-wise distribution of microfilaremic dogs revealed that 12 (36.36%), 8 (24.24%), 5 (15.15%), 4 (12.12%), 2 (6.06%), 1 (3.03%), and 1 (3.03%) cases were observed in Pomeranian, non-descript, German Shepherd, Labrador, Great Dane, Lhasa Apso, and Pug dogs, respectively. Of 10 cases of D. immitis, 5, 2, 2, and 1 were observed in Pomeranian, Labrador, non-descript, and Great Dane dogs, respectively. Cases of Dipetalonema reconditum were highest in Pomeranian (7), followed by non-descript (6), German Shepherd (5), Labrador (2), Great Dane (1), Lhasa Apso (1), and Pug (1). Age-wise distribution recorded significantly (p≤0.01) higher number of cases in adult dogs (4-14 years) for D. immitis (30.30%) and D. reconditum (39.39%). Sex-wise distribution of microfilaremic dogs showed that male (22/33, 66.66%) was more predisposed to microfilaremia rather than females (11/33, 33.34%). It is apparent from the study that the number of dogs with microfilaremia due to D. reconditum was significantly (p≤0.01) higher than that of D. immitis. The present study revealed that microfilaremia due to D. immitis and D. reconditum is prevalent in the state of Gujarat. The infection with D. immitis was associated with severe lung and cardiac pathological manifestations.


MGMT methylation status: the advent of stratified therapy in glioblastoma?
Glioblastomas are the most malignant gliomas with median survival times of only 15 months despite modern therapies. All standard treatments are palliative. Pathogenetic factors are diverse, hence, stratified treatment plans are warranted considering the molecular heterogeneity among these tumors. However, most patients are treated with "one fits all" standard therapies, many of them with minor response and major toxicities. The integration of clinical and molecular information, now becoming available using new tools such as gene arrays, proteomics, and molecular imaging, will take us to an era where more targeted and effective treatments may be implemented. A first step towards the design of such therapies is the identification of relevant molecular mechanisms driving the aggressive biological behavior of glioblastoma. The accumulation of diverse aberrations in regulatory processes enables tumor cells to bypass the effects of most classical therapies available. Molecular alterations underlying such mechanisms comprise aberrations on the genetic level, such as point mutations of distinct genes, or amplifications and deletions, while others result from epigenetic modifications such as aberrant methylation of CpG islands in the regulatory sequence of genes. Epigenetic silencing of the MGMT gene encoding a DNA repair enzyme was recently found to be of predictive value in a randomized clinical trial for newly diagnosed glioblastoma testing the addition of the alkylating agent temozolomide to standard radiotherapy. Determination of the methylation status of the MGMT promoter may become the first molecular diagnostic tool to identify patients most likely to respond that will allow individually tailored therapy in glioblastoma. To date, the test for the MGMT-methylation status is the only tool available that may direct the choice for alkylating agents in glioblastoma patients, but many others may hopefully become part of an arsenal to stratify patients to respective targeted therapies within the next years.


Diseases Neglected by the Media in Espírito Santo, Brazil in 2011-2012.
The aims of the present study were to identify and analyse the Diseases Neglected by the Media (DNMs) via a comparison between the most important health issues to the population of Espírito Santo, Brazil, from the epidemiological perspective (health value) and their effective coverage by the print media, and to analyse the DNMs considering the perspective of key journalists involved in the dissemination of health topics in the state media. Morbidity and mortality data were collected from official documents and from Health Information Systems. In parallel, the diseases reported in the two major newspapers of Espírito Santo in 2011-2012 were identified from 10,771 news articles. Concomitantly, eight interviews were conducted with reporters from the two newspapers to understand the journalists' reasons for the coverage or neglect of certain health/disease topics. Quantitatively, the DNMs identified diseases associated with poverty, including tuberculosis, leprosy, schistosomiasis, leishmaniasis, and trachoma. Apart from these, diseases with outbreaks in the period evaluated, including whooping cough and meningitis, some cancers, respiratory diseases, ischaemic heart disease, and stroke, were also seldom addressed by the media. In contrast, dengue fever, acquired immune deficiency syndrome (AIDS), diabetes, breast cancer, prostate cancer, tracheal cancer, and bronchial and lung cancers were broadly covered in the period analysed, corroborating the tradition of media disclosure of these diseases. Qualitatively, the DNMs included rare diseases, such as amyotrophic lateral sclerosis (ALS), leishmaniasis, Down syndrome, and verminoses. The reasons for the neglect of these topics by the media included the political and economic interests of the newspapers, their editorial line, and the organizational routine of the newsrooms. Media visibility acts as a strategy for legitimising priorities and contextualizing various realities. Therefore, we propose that the health problems identified should enter the public agenda and begin to be recognized as legitimate demands.


Characterization of GYP(B-A-B) hybrid glycophorins among Thai blood donors with Mia-positive phenotypes.
GYPA and GYPB genes encode the antigens of the MNS blood group system carried on glycophorin A (GPA) and glycophorin B (GPB), or on a hybrid molecule of GPA and GPB. GP hybrid variants are created through unequal crossing over and gene conversion, typically from the parent genes GYPA and GYPB. In the present study, we characterized the GYP(B-A-B) hybrid variants among Thai blood donors with Mia-positive phenotypes using PCR-based coupled to DNA sequencing techniques. Altogether, 1,020 samples from Thai blood donors were tested with anti-Mia by conventional tube technique (CTT). Polymerase chain reaction with sequence-specific primer (PCR-SSP) was initially used to differentiate normal GYPB, GYP*Vw and groups of GYP*Hut, GYP*Mur, GYP*Hop, GYP*Bun and GYP*HF alleles. Subsequently, GYP(B-A-B) hybrid variants were investigated using DNA sequencing. Among 1,020 blood donors, 127 (12.45%) were Mi(a+) phenotypes. The comparison Mia typing results between CTT and PCR-SSP were concordant. All Mi(a+) samples were positive with only group of GYP*Hut, GYP*Mur, GYP*Hop, GYP*Bun and GYP*HF alleles by PCR-SSP. Regarding the sequencing results, 115/1,020 (11.27%) donors carried the GYP*Mur, of which 111/1,020 (10.88%) were GYP*Mur/GYPB heterozygotes and the other 4/1,020 (0.39%) donors were GYP*Mur/GYP*Mur homozygotes. The remaining 12 donors included different GYP*Bun-like alleles; 11 of them (1.08%) were GYP*Thai/GYPB heterozygotes, and one (0.10%) was GYP*Thai II/GYPB heterozygotes. With 5.83% (119/2,040) of the total hybrid alleles, GYP*Mur was the predominant allele. The GYP*HF, GYP*Bun, GYP*Hop and GYP*Kip alleles were not observed in this study. Regarding the hybrid GP variants, a consensus of observed prevalent GYP*Mur and GYP*Bun-like alleles, respectively, was identified in the Thai population. The introduction of our strategy has allowed us to identify the zygosity for GYP hybrid variants, particularly GYP(B-A-B) hybrid genes, when antisera are unavailable and lacking adequate phenotypic features to determine GP variants.


An Overview of Safety Issues on Use of Insulin Pumps and Continuous Glucose Monitoring Systems in the Hospital.
Summarize safety issues related to patients using insulin pump therapy and continuous glucose monitoring systems (CGMS) in the outpatient setting when they are hospitalized and to review steps that can be taken to mitigate risk associated with use or discontinuation of these devices. Two recent consensus conferences were held on the topics of inpatient use of insulin pumps and CGMS devices. In addition to commonly known safety issues (e.g., device malfunction, infection), cybersecurity and the vulnerability of contemporary technology to hacking have emerged. CGMS capabilities offer the promise of advancing the goal for development of glucometry (centralized monitoring of real-time glucose data). Strategies to assuring safe use of insulin pumps and CGMS in the hospital include collaboration between the patient and staff, proper patient selection, and clear policies and procedures outlining safe use. Available data indicates few adverse events associated with these devices in the hospital. Current data suggests, with proper patient selection and a clear process in place for glycemic management, that adverse events are rare, and consensus favors allowing use of the technology in the hospital. The topic of insulin pump and CGMS in the hospital would greatly benefit from more institutions reporting on their experiences and prospective clinical trials.


Self-care: why do parents leave their children unsupervised?
We used a preferences-and-constraints model to develop four hypotheses to explain why parents may choose self-care (an unsupervised arrangement) as the primary child care arrangement for their children over supervised alternatives and tested them in a multivariate framework using 1995 data from the Survey of Income and Program Participation. We found that the choice of self-care over supervised care alternatives is linked to the availability of parents' time to care for children, the child's level of responsibility and maturity, and the neighborhood context. However, we found no evidence that parents' ability to pay for child care is related to the choice of self-care. The results also suggest that parents use different decision-making processes, depending on their children's ages.


Contrast Enhanced Ultrasound as a Radiation-Free Alternative to Fluoroscopic Nephrostogram for Evaluating Ureteral Patency.
We compared contrast enhanced ultrasound and fluoroscopic nephrostography in the evaluation of ureteral patency following percutaneous nephrolithotomy. This prospective cohort, noninferiority study was performed after obtaining institutional review board approval. We enrolled eligible patients with kidney and proximal ureteral stones who underwent percutaneous nephrolithotomy at our center. On postoperative day 1 patients received contrast enhanced ultrasound and fluoroscopic nephrostogram within 2 hours of each other to evaluate ureteral patency, which was the primary outcome of this study. A total of 92 pairs of imaging studies were performed in 82 patients during the study period. Five study pairs were excluded due to technical errors that prevented imaging interpretation. Females slightly predominated over males with a mean ± SD age of 50.5 ± 15.9 years and a mean body mass index of 29.6 ± 8.6 kg/m2. Of the remaining 87 sets of studies 69 (79.3%) demonstrated concordant findings regarding ureteral patency for the 2 imaging techniques and 18 (20.7%) were discordant. The nephrostomy tube was removed on the same day in 15 of the 17 patients who demonstrated antegrade urine flow only on contrast enhanced ultrasound and they had no subsequent adverse events. No adverse events were noted related to ultrasound contrast injection. While contrast enhanced ultrasound used no ionizing radiation, fluoroscopic nephrostograms provided a mean radiation exposure dose of 2.8 ± 3.7 mGy. A contrast enhanced ultrasound nephrostogram can be safely performed to evaluate for ureteral patency following percutaneous nephrolithotomy. This imaging technique was mostly concordant with fluoroscopic findings. Most discordance was likely attributable to the higher sensitivity for patency of contrast enhanced ultrasound compared to fluoroscopy.


Characteristics and Clinical Outcome of Lyme Neuroborreliosis in a High Endemic Area, 1995-2014: A Retrospective Cohort Study in Denmark.
Despite a well-described symptomatology, treatment delay and sequelae are common in patients with Lyme neuroborreliosis (LNB). The aim of this study was to contribute to the knowledge about the symptomatology and epidemiology of LNB. We conducted a retrospective study of all LNB cases verified by a positive Borrelia intrathecal antibody index test performed at the Department of Microbiology, Odense University Hospital, Denmark, from 1995 through 2014. The study included 431 patients; 126 were children. The mean incidence was 4.7 per 100 000 inhabitants per year. The median delay from neurological symptom debut to first hospital contact was 20 days and significantly longer for patients with symptom debut in the winter/early spring. The most common clinical symptoms were painful radiculitis (65.9%), cranial nerve palsy (43.4%), and headache (28.3%). A total of 30.6% were seen in >1 hospital department, and 85.6% were admitted during their course of treatment. Serum Borrelia immunoglobulin M and immunoglobulin G at the time of positive Borrelia intrathecal antibody index test were negative in 67 patients (15.5%). We found a median treatment delay of 24 days, with no improvement in our 20-year study period. Residual symptoms following treatment were found in 28.1% of patients, and risk of residual symptoms was significantly associated with delay from symptom debut to initiation of treatment. The association between treatment delay and residual symptoms and the lack of improvement in treatment delay during the study period highlight the need for standardized diagnostic routines and a better follow-up for LNB patients. Our findings disprove that all patients with LNB develop positive serum Borrelia antibodies within 6 weeks after infection.


Immune response after two doses of the novel split virion, adjuvanted pandemic H1N1 influenza A vaccine in HIV-1-infected patients.
To determine the rate of seroconversion after 2 doses of a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in human immunodeficiency virus type 1 (HIV-1)-infected patients (ClinicalTrials.gov NCT01017172). Diagnostic study of adult HIV-1-infected patients scheduled for H1N1 influenza A vaccination. Blood samples where taken before and 21 days after the first dose and 21 days after the second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and a ≥ 4-fold increase in AB titer 21 days after vaccination. One hundred thirty-five patients received 2 doses of the H1N1 vaccine and were analyzed. The rate of seroconversion was 68.2% (95% confidence interval, 59.6-75.9) after the first dose and 91.9% (95% confidence interval, 85.9-95.9) after the second dose. Patients who did not seroconvert had a lower mean nadir CD4 cell count (± standard deviation; 81 ± 99 vs 190 ± 148 cells/μL; P = .006), had a longer duration of HIV infection (± standard deviation; 13.1 ± 5.9 vs 8.8 ± 6.8 years; P = .04), and were more likely to have an AB titer ≥ 1:40 before vaccination (4% vs 55%; P < .001) when compared with patients with seroconversion. No other differences were found between the 2 groups, including AIDS status, highly active antiretroviral therapy status, HIV RNA - polymerase chain reaction load <50 copies/mL, CD4 cell count, sex, body mass index, and chronic hepatitis. Among HIV-infected patients, the rate of seroconversion after the first dose of an adjuvanted H1N1 influenza A vaccine was 68% and increased to 92% after a second doses.


Internal Medicine Residents' Perception of Cancer Prognosis.
Cancer is the second leading cause of death in the USA. Many internal medicine physicians feel uncomfortable having to prognosticate; however, oncology patients often ask this of them. The inability to provide an accurate prognosis could lead a patient to make a treatment decision incongruent with their true wishes. We conducted this study to assess resident and attending physicians' knowledge of cancer prognosis and to establish the source of residents' knowledge. We conducted a prospective, cross-sectional study to assess internal medicine resident and attending physician knowledge of median survival for seven different oncologic case scenarios. Correct answers were defined by results of randomized, phase III trials. Residents were asked to identify the source(s) of information that most significantly influenced their choices. All residents and attending physicians affiliated with the University of Hawaii were invited to participate. A total of 67 of 85 surveys (78.8%) were completed, representing 41 residents and 26 attending physicians. Overall, the respondents correctly estimated median survival 42.6% of the time. The respondents underestimated more often than overestimated median survival (46.3% vs. 14.9%, p = 0.0001). Seventy-three percent of residents cited inpatient experience as influencing their oncologic knowledge. Internal medicine residents and attending physicians correctly estimate median survival of cancer patients less than 50% of the time and often underestimate survival. Inpatient rotations, where residents care for the oncologic patients experiencing significant complications of their cancer and treatment, may be giving them an unbalanced perspective on cancer prognosis.


An improved procedure for N- to C-directed (Inverse) solid-phase peptide synthesis.
A method for solid-phase peptide synthesis in the N- to C-direction that delivers good coupling yields and a low degree of epimerization is reported. The optimized method involves the coupling, without preactivation, of the resin-bound C-terminal amino acid with excess amounts of amino acid tri-tert-butoxysilyl (Sil) esters, using HATU as coupling reagent and 2,4,6-trimethylpyridine (TMP, collidine) as a base. For the amino acids investigated, the degree of epimerization was typically 5%, except for Ser(t-Bu) which was more easily epimerized (ca. 20%). Five tripeptides (AA(1)-AA(2)-AA(3)) with different properties were used as representative model peptides in the development of the synthetic method: Asp-Leu-Glu, Leu-Ala-Phe, Glu-Asp-Val, Asp-Ser-Ile, and Asp-D-Glu-Leu. The study used different combinations of HATU and TBTU as activating agents, N, N-diisopropylethylamine (DIEA) and TMP as bases, DMF and dichloromethane as solvents, and cupric chloride as an epimerization suppressant. The epimerization of AA(2) in the coupling of AA(3) was further reduced in the presence of cupric chloride. However, the use of this reagent also resulted in a decrease in loading onto the resin and significant cleavage between AA(1) and AA(2). Experiments indicated that the observed suppressing effect of cupric chloride on epimerization in the present system merely seemed to be a result of a base-induced cleavage of the oxazolone system, the key intermediate in the epimerization process. Consequently, the cleavages were most pronounced in slow couplings. An improved synthesis of fully characterized amino acid tri-tert-butoxysilyl (Sil) ester hydrochloride building blocks is presented. The amino acid Sil esters were found to be stable as hydrochlorides but not as free bases. Although only a few peptides have been used in this study, we believe that the facile procedure devised herein should provide an attractive alternative for the solid-phase synthesis of short (six residues or less) C-terminally modified peptides, e.g., in library format.


The recovery functions of auditory event-related potentials during split-second discriminations.
We examined the recovery cycles of auditory event-related potentials (ERPs) in a high-speed auditory discrimination task and in passive conditions. Each trial contained 3 tones cued by a warning flash. In passive conditions, auditory ERPs consisted mainly of N1 (108 msec) and P2 (213 msec) components superimposed on a small CNV. The N1 and P2 were comparable in amplitude and both had prolonged refractory periods. In discriminative reaction time (DRT) conditions the same tones cued or inhibited press responses and elicited additional endogenous components (principally the Nd and P3). ERPs in DRT conditions were superimposed upon a prominent CNV that began after the warning cue and lasted throughout the signal delivery period. The N1 was larger in active than passive conditions and showed less marked refractory effects, while the P2 was smaller and showed more marked refractoriness. Differences between active and passive conditions could be explained by the presence of an endogenous negative potential (the Nd) with a short refractory period that was superimposed upon the N1 and P2. The P3 was recorded only in active conditions. At short ISIs (0.5 sec), P3 amplitudes were reduced and P3 latencies lengthened in parallel with prolongations in reaction time due to so-called psychological refractory period (PRP) effects. Both P3 recovery and the PRP reflected central mechanisms since they were observed at short ISIs when stimuli cueing different responses succeeded one another. N1 and P3 amplitudes diminished over the course of the experiment in both active and passive conditions. The decrease (amounting to about 30% of initial amplitudes) did not appear due to reductions in vigilance, since it was not accompanied by changes in reaction time or response accuracy, or by changes in other endogenous components (CNV or Nd). Short-term N1 habituation was unaffected by long-term amplitude reductions suggesting that independent mechanisms were responsible for the two phenomena.


Perioperative enhanced recovery programmes for gynaecological cancer patients.
Gynaecological malignancies contribute to 10% to 15% of cancers in women internationally. In recent years, a trend towards new perioperative care strategies has been documented as 'Fast Track (FT) surgery', or 'Enhanced Recovery Programmes' to replace some traditional approaches in surgical care. The FT multimodal programmes may enhance the postoperative recovery by means of reducing surgical stress. This systematic review aims to assess fully the beneficial and harmful effects of FT programmes in gynaecological cancer care. To evaluate the beneficial and harmful effects of FT programmes in gynaecological cancer care. We searched the following databases, The Cochrane Gynaecological Cancer Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 4, 2009, MEDLINE and EMBASE to November 2009. In addition, all reference lists of included trials were searched and experts in the gynaecological oncology community were contacted in an attempt to locate trials. This search was updated and re-run to 1 May 2012, for this update. All randomised controlled trials (RCTs) comparing any type of FT programmes for surgery in gynaecological cancer to conventional recovery strategies were included. Two review authors independently screened studies for inclusion. Since no RCTs were identified, data collection and analysis could not be performed. No studies were identified that met the inclusion criteria. We currently have no evidence from high-quality studies to support or refute the use of perioperative enhanced recovery programmes for gynaecological cancer patients. Further well-designed RCTs with standard FT programmes are needed. This review has been updated in 2012. The results of the original review published in 2010 remain unchanged.


Prosthetic anterior cruciate ligaments in the rabbit. A comparison of four types of replacement.
Four types of prosthetic replacement for the anterior cruciate ligament (carbon fibre, carbon fibre and Dacron composite, Dacron alone and bovine xenograft) were assessed at three, six and 12 months after implantation in the knees of New Zealand white rabbits. The synovium and both intra-articular and intra-osseous portions of the ligaments were examined macroscopically, by light microscopy and by scanning electron microscopy. All the knees showed mild synovitis, and there was no significant growth into the intra-articular part of any ligament. Carbon fibre and xenograft did not appear to be suitable materials in this animal model. The composite ligament showed short-term ingrowth of fibrous tissue only into the periphery of the sheath in its intra-osseous portion, whereas the Dacron ligament showed progressive fibrous tissue ingrowth with some bony incorporation of its outer fibres.


The trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias: study protocol for a cluster randomized controlled trial.
Infections are common in nursing home (NH) residents with advanced dementia but are often managed inappropriately. Antimicrobials are extensively prescribed, but frequently with insufficient evidence to support a bacterial infection, promoting the emergence of multidrug-resistant organisms. Moreover, the benefits of antimicrobials remain unclear in these seriously ill residents for whom comfort is often the goal of care. Prior NH infection management interventions evaluated in randomized clinical trials (RCTs) did not consider patient preferences and lack evidence to support their effectiveness in 'real-world' practice. This report presents the rationale and methodology of TRAIN-AD (Trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias), a parallel group, cluster RCT evaluating a multicomponent intervention to improve infection management for suspected urinary tract infections (UTIs) and lower respiratory tract infections (LRIs) among NH residents with advanced dementia. TRAIN-AD is being conducted in 28 facilities in the Boston, USA, area randomized in waves using minimization to achieve a balance on key characteristics (N = 14 facilities/arm). The involvement of the facilities includes a 3-month start-up period and a 24-month implementation/data collection phase. Residents are enrolled during the first 12 months of the 24-month implementation period and followed for up to 12 months. Individual consent is waived, thus almost all eligible residents are enrolled (target sample size, N = 410). The intervention integrates infectious disease and palliative care principles and includes provider training delivered through multiple modalities (in-person seminar, online course, management algorithms, and prescribing feedback) and an information booklet for families. Control facilities employ usual care. The primary outcome, abstracted from the residents' charts, is the number of antimicrobial courses prescribed for UTIs and LRIs per person-year alive. TRAIN-AD is the first cluster RCT testing a multicomponent intervention to improve infection management in NH residents with advanced dementia. Its findings will provide an evidence base to support the benefit of a program addressing the critical clinical and public health problem of antimicrobial misuse in these seriously ill residents. Moreover, its hybrid efficacy-effectiveness design will inform the future conduct of cluster RCTs evaluating nonpharmacological interventions in the complex NH setting in a way that is both internally valid and adaptable to the 'real-world'. ClinicalTrials.gov, NCT03244917 . Registered on 10 August 2017.


Late domain function identified in the vesicular stomatitis virus M protein by use of rhabdovirus-retrovirus chimeras.
Little is known about the mechanisms used by enveloped viruses to separate themselves from the cell surface at the final step of budding. However, small sequences in the Gag proteins of several retroviruses (L domains) have been implicated in this process. A sequence has been identified in the M proteins of rhabdoviruses that closely resembles the PPPPY motif in the L domain of Rous sarcoma virus (RSV), an avian retrovirus. To evaluate whether the PPPY sequence in vesicular stomatitis virus (VSV) M protein has an activity analogous to that of the retroviral sequence, M-Gag chimeras were characterized. The N-terminal 74 amino acids of the VSV (Indiana) M protein, including the PPPY motif, was able to replace the L domain of RSV Gag and allow the assembly and release of virus-like particles. Alanine substitutions in the VSV PPPY motif severely compromised the budding activity of this hybrid protein but not that of another chimera which also contained the RSV PPPPY sequence. We conclude that this VSV sequence is functionally homologous to the RSV L domain in promoting virus particle release, making this the first example of such an activity in a virus other than a retrovirus. Both the RSV and VSV motifs have been shown to interact in vitro with certain cellular proteins that contain a WW interaction module, suggesting that the L domains are sites of interaction with unknown host machinery involved in virus release.


Boschniakia Rossica Polysaccharide Triggers Laryngeal Carcinoma Cell Apoptosis by Regulating Expression of Bcl-2, Caspase-3, and P53.
BACKGROUND Laryngeal cancer is a malignant head and neck tumor with high morbidity and high mortality in humans. Recently, treatments with Chinese medicines and their extracts have gradually received great attention, and studies suggest that Boschniakia rossica polysaccharide (BRP) has potential anti-tumor activity. Therefore, this study investigating the role of BRP in inducing apoptosis in human laryngeal carcinoma cells. MATERIAL AND METHODS The BRP was extracted with organic solvent and HR column. We treated Hep2 laryngeal carcinoma cells with different concentrations of BRP, then assessed cell growth inhibition rate by flow cytometry and apoptosis index by TUNEL staining. The protein expression of p53, Bcl-2, Bax, and caspase-3 were analyzed by Western blot. RESULTS Flow cytometry results showed that BRP inhibited Hep2 cell proliferation in a dose-dependent manner (p<0.05), and TUNEL staining indicated that BRP significantly increased Hep2 apoptosis index (p<0.05). Western blot results showed that the expression levels of p53 and activation of caspase-3 in Hep2 cells were significantly up-regulated (p<0.05), while the expression of Bcl-2 was significantly down-regulated (p<0.05). CONCLUSIONS BRP might induce cell apoptosis by regulating the expression level of cell apoptosis-associated proteins, suggesting strong anti-laryngeal cancer activity.


Older adults' coping strategies during the COVID-19 pandemic - a longitudinal mixed-methods study.
Older age is a main risk factor for severe COVID-19. In 2020, a broad political debate was initiated as to what extent older adults need special protection and isolation to minimize their risk for SARS-CoV-2 infection. However, isolation might also have indirect negative psychological (e.g., loneliness, stress, fear, anxiety, depression) or physical (e.g., lack of exercise, missing medical visits) consequences depending on individual strategies and personality traits to cope longitudinally with this crisis. To examine the impact of individuals' coping with the pandemic on mental health, a large sample of 880 older adults of the prospective longitudinal cohort TREND study were surveyed six times about their individual coping strategies in the COVID-19 pandemic between May 2020 (05/2020: Mage = 72.1, SDage = 6.4, Range: 58-91 years) and November 2022 in an open response format. The relevant survey question was: "What was helpful for you to get through the last months despite the COVID-19 pandemic? E.g., phone calls, going for a walk, or others." In total, we obtained 4,561 records containing 20,578 text passages that were coded and assigned to 427 distinct categories on seven levels based on qualitative content analysis using MAXQDA. The results allow new insights into the impact of personal prerequisites (e.g., value beliefs, living conditions), the general evaluation of the pandemic (e.g., positive, irrelevant, stressful) as well as the applied coping strategies (e.g., cognitive, emotional- or problem-focused) to deal with the COVID-19 pandemic by using an adapted Lazarus stress model. Throughout the pandemic emotional-focused as well as problem-focused strategies were the main coping strategies, whereas general beliefs, general living conditions and the evaluation were mentioned less frequently.


The new challenges for chemotherapy research.
Scientific knowledge is constantly expanding, and needs are changing; therefore, efforts must be made to adapt the treatment of leprosy and the manner in which it is implemented to the newly identified needs. Because an effective vaccine against leprosy remains to be identified, multidrug therapy (MDT) is the only tool available for leprosy control. At present, therefore, the priority is to make MDT available in all endemic countries for all patients, even those living in difficult-to-access areas. The remaining important issues in chemotherapy research are to improve the quality of leprosy case-finding, improve the quality of MDT, identify the areas in which leprosy patients are not receiving proper MDT, and find the means necessary to ensure delivery to all of appropriate MDT. The MDT regimens recommended by the World Health Organization are of too long duration, require correct classification of the patients as PB or MB, and rely upon the daily self-administration of dapsone and clofazimine to prevent selection of rifampicin resistant mutants among MB patients. Thus, research leading to the development of new drug regimens should be directed toward overcoming the shortcomings of the presently recommended regimens. The drugs required to permit use of regimens of shorter duration, that may be employed among both PB and MB patients, and that enable fully supervised drug administration may be already in hand, and the necessary clinical trials to confirm efficacy and acceptability should be carried out.


The mechanobiology of articular cartilage development and degeneration.
The development, maintenance, and destruction of cartilage are regulated by mechanical factors throughout life. Mechanical cues in the cartilage fetal endoskeleton influence the expression of genes that guide the processes of growth, vascular invasion, and ossification. Intermittent fluid pressure maintains the cartilage phenotype whereas mild tension (or shear) promotes growth and ossification. The articular cartilage thickness is determined by the position at which the subchondral growth front stabilizes. In mature joints, cartilage is thickest and healthiest where the contact pressure and cartilage fluid pressure are greatest. The depth-dependent histomorphology reflects the local fluid pressure, tensile strain, and fluid exudation. Osteoarthritis represents the final demise and loss of cartilage in the skeletal elements. The initiation and progression of osteoarthritis can follow many pathways and can be promoted by mechanical factors including: (1) reduced loading, which activates the subchondral growth front by reducing fluid pressure; (2) blunt impact, causing microdamage and activation of the subchondral growth front by local shear stress; (3) mechanical abnormalities that increase wear at the articulating surface; and (4) other mechanically related factors. Research should be directed at integrating our mechanical understanding of osteoarthritis pathogenesis and progression within the framework of cellular and molecular events throughout ontogeny.


Nanobased Platforms for Diagnosis and Treatment of COVID-19: From Benchtop to Bedside.
Human respiratory viral infections are the leading cause of morbidity and mortality around the world. Among the various respiratory viruses, coronaviruses (e.g., SARS-CoV-2) have created the greatest challenge and most frightening health threat worldwide. Human coronaviruses typically infect the upper respiratory tract, causing illnesses that range from common cold-like symptoms to severe acute respiratory infections. Several promising vaccine formulations have become available since the beginning of 2021. Nevertheless, achievement of herd immunity is still far from being realized. Social distancing remains the only effective measure against SARS-CoV-2 infection. Nanobiotechnology enables the design of nanobiosensors. These nanomedical diagnostic devices have opened new vistas for early detection of viral infections. The present review outlines recent research on the effectiveness of nanoplatforms as diagnostic and antiviral tools against coronaviruses. The biological properties of coronavirus and infected host organs are discussed. The challenges and limitations encountered in combating SARS-CoV-2 are highlighted. Potential nanodevices such as nanosensors, nanobased vaccines, and smart nanomedicines are subsequently presented for combating current and future mutated versions of coronaviruses.


Comparisons of Airborne Measurements and Inventory Estimates of Methane Emissions in the Alberta Upstream Oil and Gas Sector.
Airborne measurements of methane emissions from oil and gas infrastructure were completed over two regions of Alberta, Canada. These top-down measurements were directly compared with region-specific bottom-up inventories that utilized current industry-reported flaring and venting volumes (reported data) and quantitative estimates of unreported venting and fugitive sources. For the 50 × 50 km measurement region near Red Deer, characterized by natural gas and light oil production, measured methane fluxes were more than 17 times greater than that derived from directly reported data but consistent with our region-specific bottom-up inventory-based estimate. For the 60 × 60 km measurement region near Lloydminster, characterized by significant cold heavy oil production with sand (CHOPS), airborne measured methane fluxes were five times greater than directly reported emissions from venting and flaring and four times greater than our region-specific bottom up inventory-based estimate. Extended across Alberta, our results suggest that reported venting emissions in Alberta should be 2.5 ± 0.5 times higher, and total methane emissions from the upstream oil and gas sector (excluding mined oil sands) are likely at least 25-50% greater than current government estimates. Successful mitigation efforts in the Red Deer region will need to focus on the >90% of methane emissions currently unmeasured or unreported.


"Skinless wonders": Body Worlds and the Victorian freak show.
In 2002, Gunther von Hagens's display of plastinated corpses opened in London. Although the public was fascinated by Body Worlds, the media largely castigated the exhibition by dismissing it as a resuscitated Victorian freak show. By using the freak show analogy, the British press expressed their moral objection to this type of bodily display. But Body Worlds and nineteenth-century displays of human anomalies were linked in more complex and telling ways as both attempted to be simultaneously entertaining and educational. This essay argues that these forms of corporeal exhibitionism are both examples of the dynamic relationship between the popular and professional cultures of the body that we often erroneously think of as separate and discrete. By reading Body Worlds against the Victorian freak show, I seek to generate a fuller understanding of the historical and enduring relationship between exhibitionary culture and the discourses of science, and thus to argue that the scientific and the spectacular have been, and clearly continue to be, symbiotic modes of generating bodily knowledge.


Control of retinal information coding by GABAB receptors.
The directional selectivity of amacrine and ganglion cells was studied using conventional intracellular recording techniques and drug application in the superfused retina-eyecup preparation of the tiger salamander. Baclofen, a GABAB receptor agonist, enhanced normal directional responses in some directionally selective third-order neurons. In about 30% of the cells that were not normally directional, baclofen induced direction-selective responses. This effect was particularly marked when 2-amino-4-phosphonobutyrate (APB) was used to isolate the OFF pathway. Comparisons of the effects of APB and baclofen on induced directional cells indicate that directional information in the ON and OFF channels is often handled separately and frequently is not aligned. This tends to obscure the observation of directionality as seen from the soma. Application of picrotoxin blocked both normal directional selectivity and baclofen-induced directional selectivity in some cells. Superfusion of picrotoxin and strychnine together blocked directionality in almost all cells. In both normal and induced directionality, the null direction response varied from cell to cell between a small depolarization, no voltage response, or a hyperpolarization. Injection of positive current often revealed "silent" inhibition. Some induced direction-selective cells did not show any evidence of inhibition in the null direction. The similarities in the response to baclofen, the influence of GABA and glycine antagonists, and the characteristics of the null-direction responses suggest that both normal and induced directionality originate from the same sources or mechanisms. Baclofen also induced orientation selectivity, but this was rarely observed.


Putting on Academic Armor: How Black Physicians and Trainees Take Stances to Make Racism Visible Amid Publishing Constraints.
Starting with reflexivity: As a Black woman medical student at a predominately white institution, a white woman full professor and deputy editor-in-chief of a journal, and a white woman associate professor with a deep interest in language, we understand that medicine and medical education interpellate each of us as a particular kind of subject. As such, we begin with a narrative grounding in our personal stances. Phenomenon: While there are a growing number of empirical studies of Black physicians' and trainees' experiences of racism, there are still few accounts from a first-person perspective. Black authors of these personal commentaries or editorials, who already experience microaggressions and racial trauma in their work spaces, must put on their academic armor to further experience them in publishing spaces. This study seeks to understand the stances Black physicians and trainees take as they share their personal experiences of racism. Approach: We searched four databases, identifying 29 articles authored by Black physicians and trainees describing their experiences. During initial analysis, we identified and coded for three sets of discursive strategies: identification, intertextuality, and space-time. Throughout the study, we reflected on our own stances in relation to the experience of conducting the study and its findings. Findings: Authors engaged in stance-taking, which aligned with the concept of donning academic armor, by evaluating and positioning themselves with respect to racism and the norms of academic discourse in response to ongoing conversations both within medicine and in the broader U.S. culture. They did this by (a) positioning themselves as being Black and, therefore, qualified to notice and name personal racist experiences while also aligning themselves with the reader through shared professional experiences and goals; (b) intertextual connections to other related events, people, and institutions that they-and their readers-value; and (c) aligning themselves with a hoped-for future rather than a racist present. Personal insights: Because the discourses of medicine and medical publishing interpellate Black authors as Others they must carefully consider the stances they take, particularly when naming racism. The academic armor they put on must be able to not only defend them from attack but also help them slip unseen through institutional bodies replete with mechanisms to eject them. In addition to analyzing our own personal stance, we leave readers with thought-provoking questions regarding this armor as we return to narrative grounding.


African swine fever virus DNA: restriction endonuclease cleavage patterns of wild-type, Vero cell-adapted and plaque-purified virus.
DNA from African swine fever (ASF) virus was isolated and was characterized by two restriction enzymes, SmaI and EcoRI. Although both enzymes can distinguish Vero cell-adapted ASF isolates by characteristic restriction endonuclease cleavage patterns, all ASF isolates examined exhibited a high degree of similarity, as measured by co-migration of most of the DNA fragments. The molecular weight of ASF DNA, based on size estimates of DNA fragments from cleavage patterns, ranged from 93 x 10(6) to 100 x 10(6). Virus genome heterogeneity was observed in uncloned, cell culture-adapted ASF isolates as well as in a plaque-purified virus after serial passage in Vero cells. In contrast to the rather minor differences in restriction pattern among the Vero cell-adapted isolates, a major alteration in restriction endonuclease cleavage sites was observed during adaptation of the wild-type virus to cell culture.


Surgical management of recurrent pancreatitis in children with pancreas divisum.
To analyze an institutional experience with pancreatitis in childhood to clarify the frequency of pancreas divisum in that patient population, the characteristics of pancreatitis in children with pancreas divisum, and the role of surgical management in their treatment. The role of pancreas divisum in causing acute and relapsing pancreatitis and chronic, recurring abdominal pain is controversial. Although the anatomical abnormality is present from birth, most investigators have reported cases with onset of symptoms in adulthood. The reported pediatric experience with this disorder is small, and the natural history of pancreatitis in children with pancreas divisum has not been well elucidated. A retrospective chart review of all children 18 years of age and younger with a discharge diagnosis of pancreatitis identified 135 patients treated in the authors' institution from 1978 to 1998. Ten patients were found to have anatomical variants of pancreas divisum associated with recurrent or chronic pancreatitis. The medical records of these patients were reviewed for data on the presentation, diagnostic findings, imaging studies, treatment, surgical findings, and pathologic findings in these children. Chart review and telephone calls were used to assess the current state of health in nine patients available for follow-up. Pancreas divisum was identified in 7.4% of all children with pancreatitis and 19.2% of children with relapsing or chronic pancreatitis. Patients had early onset of recurrent episodic epigastric pain and vomiting, at a mean age of 6 years. Three patients had a positive family history of pancreatitis and one was proven by DNA analysis to have hereditary pancreatitis. Pancreatitis was documented by elevated amylase or lipase levels, and endoscopic retrograde cholangiopancreatography was the method of diagnosis of pancreas divisum in all patients. Eight patients had complete pancreas divisum and two had incomplete variants. Eight patients underwent surgery to improve ductal drainage. Seven underwent transduodenal sphincteroplasty of the accessory papilla, along with sphincteroplasty of the major papilla in two (plus septoplasty in one). Three patients underwent longitudinal pancreaticojejunostomy, as a primary procedure in one patient with midductal stenosis and in two because of recurring pancreatitis after sphincteroplasty. The surgical findings and histologic examination of five patients undergoing distal pancreatectomy revealed striking changes of advanced chronic pancreatitis. Patients responding to sphincteroplasty alone showed less severe histologic changes. Overall, three of seven patients had excellent results, three were improved, and one had continued disabling attacks of pancreatitis. The mean duration of follow-up was 7.3 years, and there were no deaths. No patients had endocrine or exocrine pancreatic insufficiency, and none required chronic analgesics. Pancreas divisum is an important cause of recurrent pancreatitis in childhood and should be sought aggressively in children with more than one episode of pancreatitis or pancreatitis with a history of chronic recurrent abdominal pain. Surgical intervention is directed toward relief of ductal obstruction and may involve accessory duct sphincteroplasty alone or in combination with major sphincteroplasty and septoplasty. Patients with more distal ductal obstruction or ductal ectasia may benefit from pancreaticojejunostomy.